Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, 148 Guro-dong, Guro-gu, Seoul 08308, Korea.
Department of Industrial Management Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea.
Int J Mol Sci. 2018 Nov 15;19(11):3602. doi: 10.3390/ijms19113602.
In this study, a novel three-dimensional (3D) bone morphogenic protein-2 (BMP-2)-delivering tannylated polycaprolactone (PCL) (BMP-2/tannic acid (TA)/PCL) scaffold with anti-oxidant, anti-inflammatory, and osteogenic activities was fabricated via simple surface coating with TA, followed by the immobilization of BMP-2 on the TA-coated PCL scaffold. The BMP-2/TA/PCL scaffold showed controlled and sustained BMP-2 release. It effectively scavenged reactive oxygen species (ROS) in cells, and increased the proliferation of MC3T3-E1 cells pre-treated with hydrogen peroxide (H₂O₂). Additionally, the BMP-2/TA/PCL scaffold significantly suppressed the mRNA levels of pro-inflammatory cytokines, including matrix metalloproteinases-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in lipopolysaccharide (LPS)-induced MC3T3-E1 cells. Furthermore, it showed outstanding enhancement of the osteogenic activity of MC3T3-E1 cells through increased alkaline phosphatase (ALP) activity and calcium deposition. Our findings demonstrated that the BMP-2/TA/PCL scaffold plays an important role in scavenging ROS, suppressing inflammatory response, and enhancing the osteogenic differentiation of cells.
在这项研究中,通过简单的表面涂覆单宁酸(TA),随后将骨形态发生蛋白-2(BMP-2)固定在 TA 涂层的聚己内酯(PCL)支架上,制备了具有抗氧化、抗炎和成骨活性的新型三维(3D)BMP-2 递药单宁酸(TA)/聚己内酯(PCL)(BMP-2/TA/PCL)支架。BMP-2/TA/PCL 支架表现出控制和持续的 BMP-2 释放。它可以有效清除细胞内的活性氧(ROS),并增加预先用过氧化氢(H₂O₂)处理的 MC3T3-E1 细胞的增殖。此外,BMP-2/TA/PCL 支架显著抑制了脂多糖(LPS)诱导的 MC3T3-E1 细胞中促炎细胞因子的 mRNA 水平,包括基质金属蛋白酶-3(MMP-3)、环氧化酶-2(COX-2)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。此外,它通过增加碱性磷酸酶(ALP)活性和钙沉积,显著增强了 MC3T3-E1 细胞的成骨活性。我们的研究结果表明,BMP-2/TA/PCL 支架在清除 ROS、抑制炎症反应和增强细胞成骨分化方面发挥着重要作用。